Spinnaker, an application in Spiral’s study manifest, has recently been used in the long-awaited TTM2 trial. After successful resuscitation, patients who survive a cardiac arrest often remain severely ill and require intensive care. Controlling body temperature is a potential treatment that may prevent brain damage. The TTM2-trial aimed to study the impact on all-cause mortality of targeted hypothermia compared with targeted normothermia.

1900 adults were enrolled with a coma after an out of hospital cardiac arrest with a presumed cardiac or unknown cause. 

They were assigned to hypothermia at 33°C followed by controlled rewarming OR to normothermia with early treatment of fever (body temp ≥37.8°C) 

The primary endpoint was death from any cause at six months. 

Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale 

In the 33°C arm “gold standard” therapeutic hypothermia was aimed for with cooling initiated early, slow rewarming, and care taken to avoid rebound fever. 

In the early treatment of fever arm, fewer than half of the patients were cooled with a cooling device. 

There was substantial separation in temperature by treatment group and the hypothermia arm was likely as good as can be achieved in clinical practice

Some of the patients in the normothermia group developed fever and the temperatures in this group were broadly similar to those recorded in the control group of the pivotal Hypothermia after Cardiac Arrest trial in which no temperature management was used.

Despite this, at 6 months, 50% in the hypothermia group and 48% in the normothermia group had died (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). 

At 6 months, a total of 54% in the hypothermia group and 54% in the normothermia group had a poor functional outcome (relative risk in the hypothermia group, 1.00; 95% CI, 0.91 to 1.08). 

Pre-specified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. 

There was no evidence that therapeutic hypothermia benefited any patient subgroup in terms of death or disability

In fact, Therapeutic hypothermia was associated with a significantly higher risk of arrhythmia resulting in hemodynamic compromise. 

With the above supporting the conclusions of the trial, the TTM2 data should herald the end of the era of therapeutic hypothermia for adult cardiac arrest.

Spiral is proud to be associated with this collaboration and congratulate the teams on their ability to work together to help improve the outcomes of cardiac arrest. These are some truly astounding results.

Dive deeper:

• The New England Journal of Medicine Publication 

• Paul Young’s TTM2 Tweet thread 

• Trial Results Meeting Online at Critical Care Reviews

• Celia Bradfords review in The Bottom Line

The TTM2 Website